rs2393967

Variant names:

• chr10-63373396-A-C
• rs2393967
• NM_032776.3:c.333+6922T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-63373396-A-C
• chr10-63373396-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032776.3(JMJD1C):​c.333+6922T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,194 control chromosomes in the GnomAD database, including 5,072 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5072 hom., cov: 33)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.921
• Publications: 38 publications found

Genes affected

JMJD1C (HGNC:12313): (jumonji domain containing 1C) The protein encoded by this gene interacts with thyroid hormone receptors and contains a jumonji domain. It is a candidate histone demethylase and is thought to be a coactivator for key transcription factors. It plays a role in the DNA-damage response pathway by demethylating the mediator of DNA damage checkpoint 1 (MDC1) protein, and is required for the survival of acute myeloid leukemia. Mutations in this gene are associated with Rett syndrome and intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

JMJD1C Gene-Disease associations (from GenCC):

• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JMJD1C	NM_032776.3	c.333+6922T>G		intron_variant	Intron 2 of 25	ENST00000399262.7	NP_116165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JMJD1C	ENST00000399262.7	c.333+6922T>G		intron_variant	Intron 2 of 25	5	NM_032776.3	ENSP00000382204.2
JMJD1C	ENST00000633035.1	n.278+6922T>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35274 AN: 152076 Hom.: 5077 Cov.: 33

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.232 AC: 35255 AN: 152194 Hom.: 5072 Cov.: 33 AF XY: 0.232 AC XY: 17272 AN XY: 74390

African (AFR) AF: 0.0585 AC: 2433 AN: 41562

American (AMR) AF: 0.212 AC: 3239 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1245 AN: 3468

East Asian (EAS) AF: 0.273 AC: 1414 AN: 5184

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4822

European-Finnish (FIN) AF: 0.308 AC: 3258 AN: 10572

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21571 AN: 67992

Other (OTH) AF: 0.252 AC: 531 AN: 2110

Alfa AF: 0.292 Hom.: 29874

Bravo AF: 0.216

Asia WGS AF: 0.246 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.61
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2393967; hg19: chr10-65133156;